Landscape of long interspersed element-1 and Alu chimeric transcripts in breast tumors

Introduction: Long interspersed element-1 (L1) and Alu elements are reported to regulate tumor development and progression by forming chimeric transcripts with diverse sequences. While these elements have been implicated in various cancers, the landscape of chimeric transcript formation in breast cancer remains poorly characterized. Objective: Therefore, in this study, we comprehensively investigated the profiles of L1 and Alu chimeric transcripts in breast tumors by analyzing RNA sequences from The Cancer Genome Atlas (TCGA) database. Methods: More than 50 billion paired-end RNA sequencing reads from 606 primary breast tumor tissues and 59 matched adjacent normal tissues from the TCGA database were aligned to L1 and Alu consensus sequences with Bowtie2 software and further analyzed. Results: Our analysis revealed significantly elevated expression levels of L1 and Alu retrotransposons in breast tumor tissues compared to adjacent non-tumor tissues. Importantly, higher expression of L1 and Alu in breast tumors was associated with poorer 10-year overall survival, suggesting their potential as prognostic biomarkers. Further exploration demonstrated that L1 and Alu were extensively expressed in chimeric form with adjacent transcripts. A significant difference in the frequency of 651 L1-mRNA and 1,525 Alu-mRNA chimeric transcripts was observed between non-tumor and tumor tissues. Similarly, 1,009 L1-long non-coding RNA (lncRNA) and 2,575 Alu-lncRNA chimeric transcripts exhibited significantly different frequencies between non-tumor and tumor tissues. Functional enrichment analysis revealed that these differentially expressed chimeric genes played crucial roles in multiple facets of tumorigenesis, including metabolism, signal transduction, immunity, cell cycle regulation, and apoptosis. Conclusion: Our findings demonstrate that Chimeric transcript formation with L1 and Alu retrotransposons represents a widespread phenomenon in breast cancer that impacts multiple oncogenic pathways. These results significantly expand our understanding of retrotransposon involvement in breast cancer and highlight potential novel targets for diagnostic and therapeutic development.